Genetic studies have investigated the pathogenesis of age-related macular degeneration (AMD). The pachychoroid concept has recently garnered attention as a possible explanation for AMD pathogenesis; the genetic characteristics of pachychoroid diseases have also been elucidated. In this review, we summarize previously reported genetic characteristics of AMD and pachychoroid diseases, and analyze these data to understand the pathogenesis of AMD and pachychoroid diseases. Previous studies show that VIPR2 and the CFH I62V A allele promote development of pachychoroid and central serous chorioretinopathy (CSC), while the CFH I62V G allele promotes development of drusen, pachychoroid neovasculopathy (PCN/PNV), and AMD. ARMS2/HTRA1 also promotes development of drusen, PCN/PNV, and AMD. TNFRSF10A and GATA5 are associated with CSC but not with pachychoroid, and TNFRSF10A is associated with AMD that includes PCN/PNV. These genetic characteristics suggest the following mechanisms of developing AMD and pachychoroid diseases. VIPR2 and the CFH I62V A allele promote pachychoroid development, which can result in CSC development. The CFH I62V G allele promotes a common step during PCN/PNV and AMD development induced by pachychoroid or drusen, such as damage of Bruch's membrane or retinal pigment epithelium (RPE). ARMS2/HTRA1 also promotes damage of Bruch's membrane or RPE, while the association with drusen formation is stronger in ARMS2/HTRA1 than in CFH. TNFRSF10A and GATA5 promote blood-retinal-barrier breakdown to induce CSC, which could lead to PCN/PNV development. Furthermore, recently reported genetic associations with the natural course of CSC suggest the importance of reconsidering the subtype classification of CSC. These associations would enable the development of personalized/precision medicine for CSC and.
Keywords: Age-related macular degeneration; Genetic association; Pachychoroid disease; Pathogenesis.